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Introduction <p>This real-world study compared time-to-next-treatment (TTNT), time-to-castration resistance (TTCR), and overall survival between patients with <i>BRCA1/2</i>-positive (<i>BRCA</i>+) and homologous recombination repair-negative (HRR–) metastatic castration-sensitive prostate cancer (mCSPC).</p> Methods <p>Patients who received a genetic test and initiated treatment for mCSPC (index date) after 1/1/2018 were selected from the Flatiron Health-Foundation Medicine, Inc. Metastatic PC Clinico-Genomic Database (1/1/2017–12/31/2022). Outcomes were compared between patients with&#xa0;≥&#xa0;1 positive BRCA test (<i>BRCA</i>+) and those without detected HRR mutations (HRR−) using weighted Kaplan–Meier analyses and Cox proportional hazards models after baseline characteristics (12 months pre-index) were balanced using inverse-probability of treatment weighting.</p> Results <p>In total, 149 patients with <i>BRCA</i>+&#xa0;and 1066 with HRR− mCSPC were included. Baseline characteristics were well-balanced after weighting. By 24 months after treatment initiation, a significantly higher proportion of the <i>BRCA</i>+&#xa0;than the HRR− cohort progressed to next treatment [69.7% vs. 56.8%; hazard ratio (HR)&#xa0;=&#xa0;1.45 (95% confidence interval (CI)&#xa0;1.10, 1.92), <i>p</i>&#xa0;=&#xa0;0.009]; median TTNT was shorter in the <i>BRCA</i>+&#xa0;than the HRR− cohort (10.9 vs. 18.7 months). By 24 months, a significantly higher proportion of the <i>BRCA</i>+&#xa0;than the HRR− cohort progressed to castration resistance [72.2% vs. 61.4%; HR&#xa0;=&#xa0;1.46 (95% CI&#xa0;1.16, 1.84), <i>p</i>&#xa0;=&#xa0;0.001]; median TTCR was shorter in the <i>BRCA</i>+&#xa0;than HRR− cohort (12.9 vs. 16.9 months). Numerically fewer patients in the <i>BRCA</i>+&#xa0;than the HRR− cohort survived 24 months after PC diagnosis [80.6% vs. 85.4%; HR&#xa0;=&#xa0;1.46 (95% CI&#xa0;0.99, 2.14), <i>p</i>&#xa0;=&#xa0;0.054].</p> Conclusion <p>Findings demonstrate worse outcomes for patients with <i>BRCA</i>+&#xa0;mCSPC treated with available advanced therapies, supporting the need for effective genetically targeted therapies in this population.</p>

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Comparison of Real-World Outcomes between Patients with BRCA1/2-Positive and Homologous Recombination Repair-Negative Metastatic Castration-Sensitive Prostate Cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月17日

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  • Mehmet A. Bilen,
  • Sabree Burbage,
  • Carmine Rossi,
  • Ibrahim Khilfeh,
  • Lilian Diaz,
  • Yuxi Wang,
  • Dominic Pilon,
  • Gordon Brown,
  • Neal Shore,
  • Benjamin Lowentritt,
  • Daniel W. Lin

摘要

Introduction

This real-world study compared time-to-next-treatment (TTNT), time-to-castration resistance (TTCR), and overall survival between patients with BRCA1/2-positive (BRCA+) and homologous recombination repair-negative (HRR–) metastatic castration-sensitive prostate cancer (mCSPC).

Methods

Patients who received a genetic test and initiated treatment for mCSPC (index date) after 1/1/2018 were selected from the Flatiron Health-Foundation Medicine, Inc. Metastatic PC Clinico-Genomic Database (1/1/2017–12/31/2022). Outcomes were compared between patients with ≥ 1 positive BRCA test (BRCA+) and those without detected HRR mutations (HRR−) using weighted Kaplan–Meier analyses and Cox proportional hazards models after baseline characteristics (12 months pre-index) were balanced using inverse-probability of treatment weighting.

Results

In total, 149 patients with BRCA+ and 1066 with HRR− mCSPC were included. Baseline characteristics were well-balanced after weighting. By 24 months after treatment initiation, a significantly higher proportion of the BRCA+ than the HRR− cohort progressed to next treatment [69.7% vs. 56.8%; hazard ratio (HR) = 1.45 (95% confidence interval (CI) 1.10, 1.92), p = 0.009]; median TTNT was shorter in the BRCA+ than the HRR− cohort (10.9 vs. 18.7 months). By 24 months, a significantly higher proportion of the BRCA+ than the HRR− cohort progressed to castration resistance [72.2% vs. 61.4%; HR = 1.46 (95% CI 1.16, 1.84), p = 0.001]; median TTCR was shorter in the BRCA+ than HRR− cohort (12.9 vs. 16.9 months). Numerically fewer patients in the BRCA+ than the HRR− cohort survived 24 months after PC diagnosis [80.6% vs. 85.4%; HR = 1.46 (95% CI 0.99, 2.14), p = 0.054].

Conclusion

Findings demonstrate worse outcomes for patients with BRCA+ mCSPC treated with available advanced therapies, supporting the need for effective genetically targeted therapies in this population.